Floppy closing door epiglottis treated successfully with an mhealth application based on myofunctional therapy: a case report

We introduce the first case reported to date of a floppy closing door epiglottis in an OSA (obstructive sleep apnea) patient treated successfully with an Mhealth smartphone application based on myofunctional therapy

Human Metastatic Cholangiocarcinoma Patient-Derived Xenografts and Tumoroids for Preclinical Drug Evaluation

Human metastatic cholangiocarcinoma; Xenografts; TumoroidsColangiocarcinoma metastàtic humà; Xenoempelts; TumoroidesColangiocarcinoma metastásico humano; Xenoinjertos; TumoroidesPurpose: Cholangiocarcinoma (CCA) is usually diagnosed at advanced stages, with limited therapeutic options. Preclinical models focused on unresectable metastatic CCA are necessary to develop rational treatments. Pathogenic mutations in IDH1/2, ARID1A/B, BAP1, and BRCA1/2 have been identified in 30%–50% of patients with CCA. Several types of tumor cells harboring these mutations exhibit homologous recombination deficiency (HRD) phenotype with enhanced sensitivity to PARP inhibitors (PARPi). However, PARPi treatment has not yet been tested for effectiveness in patient-derived models of advanced CCA. Experimental Design: We have established a collection of patient-derived xenografts from patients with unresectable metastatic CCA (CCA_PDX). The CCA_PDXs were characterized at both histopathologic and genomic levels. We optimized a protocol to generate CCA tumoroids from CCA_PDXs. We tested the effects of PARPis in both CCA tumoroids and CCA_PDXs. Finally, we used the RAD51 assay to evaluate the HRD status of CCA tissues. Results: This collection of CCA_PDXs recapitulates the histopathologic and molecular features of their original tumors. PARPi treatments inhibited the growth of CCA tumoroids and CCA_PDXs with pathogenic mutations of BRCA2, but not those with mutations of IDH1, ARID1A, or BAP1. In line with these findings, only CCA_PDX and CCA patient biopsy samples with mutations of BRCA2 showed RAD51 scores compatible with HRD. Conclusions: Our results suggest that patients with advanced CCA with pathogenic mutations of BRCA2, but not those with mutations of IDH1, ARID1A, or BAP1, are likely to benefit from PARPi therapy. This collection of CCA_PDXs provides new opportunities for evaluating drug response and prioritizing clinical trials.This work was supported by grants from the Fundació Marató TV3 awarded to T. Macarulla, M. Melé, and S. Peiró; BeiGene research grant awarded to T. Macarulla and S. Peiró; AECC (INVES20036TIAN), Ramón y Cajal investigator program (RYC2020-029098-I), Proyecto de I+D+i (PID2019-108008RJ-I00), and FERO Foundation grant awarded to T.V. Tian; Proyecto de Investigación en Salud from the Instituto de Salud Carlos III (ISCIII) (PI20/00898) awarded to T. Macarulla; FIS/FEDER from the Instituto de Salud Carlos III (ISCIII) (PI12/01250; CP08/00223; PI16/00253 and CB16/12/00449) awarded to S. Peiró; and Ramón y Cajal investigator program (RYC-2017-22249) awarded to M. Melé. Q. Serra-Camprubí is a recipient of the Ph.D. fellowship from La Caixa Foundation (LCF/PR/PR12/51070001). A. Llop-Guevara was supported by the AECC (INVES20095LLOP) and V. Serra by the ISCIII (CPII19/00033). E.J. Arenas was funded by the AECC (POSTD211413AREN). J. Arribas is funded by the Instituto de Salud Carlos III (AC15/00062, CB16/12/00449, and PI22/00001). This publication is based upon the work of COST Action CA18122, European Cholangiocarcinoma Network, supported by the COST (European Cooperation in Science and Technology, www.cost.eu), a funding agency for research and innovation networks. The authors would like to thank Dr. V.A. Raker for manuscript editing and Drs. N. Herranz and J. Mateo for scientific discussions. The authors acknowledge the infrastructure and support of the FERO Foundation, La Caixa Foundation, and the Cellex Foundation

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Tongue peak pressure: a tool to aid in the identification of obstruction sites in patients with obstructive sleep apnea/hypopnea syndrome

Purpose of this study was to evaluate whether tongue peak pressure measured using the Iowa Oral Performance Instrument is correlated with the topographic site of obstruction in patients with obstructive sleep apnea/hypopnea syndrome observed during drug-induced sleep endoscopy. Thirty-five consecutive adult patients (29 men, 6 women) were prospectively enrolled after having been diagnosed with severe obstructive sleep apnea/hypopnea syndrome by polysomnography. An apnea–hypopnea index > 30 was confirmed, and age, gender, and body mass index were recorded by Epworth Sleepiness Scale questionnaire, and a thorough evaluation of the upper airway by video-flexible endoscopy. Twenty healthy controls according to age and ex were chosen for IOPI measurements. After drug-induced sleep endoscopy, a topographic diagnosis was done using the VOTE classification. Tongue and lip peak pressures were both measured using the Iowa Oral Performance Instrument in all patients and in 20 healthy controls. Main outcomes and measures: the correlations between office findings, Iowa Oral Performance Instrument measures, and the VOTE tongue classification during drug-induced sleep endoscopy (T0, T1, T2) were then investigated. Results The average Iowa Oral Performance Instrument tongue and lip pressure were 44.02 ± 12.29 and 15.03 ± 3.71 kPa, respectively. The Iowa Oral Performance Instrument scores were both significantly lower than values in healthy controls (P < 0.001). The VOTE classification referring to the tongue position was T0 in 13 cases (37.1%), T1 in 12 cases (34.3%), and T2 in 10 cases (28.6%). A significant correlation was found between the Iowa Oral Performance Instrument tongue pressure and the T size during drug-induced sleep endoscopy (Kruskal–Wallis χ2 25.82; P ≤ 0.001). Conclusions In our experience, the Iowa Oral Performance Instrument is a useful tool for evaluating tongue collapse for the topographic diagnosis of patients with obstructive sleep apnea/hypopnea syndrome

Long-Term Follow-Up After Fat Graft Myringoplasty: Do Size and Location Matter?

To assess clinical and functional outcomes of a fat graft myringoplasty under local in an office setting. Prospective case series. Tertiary care facility. Patients with a tympanic membrane (TM) perforation presenting between December 2005 and June 2019. Inclusion criteria included perforation size >25% of the surface of the pars tensa of the TM, entire perforation margins visualized through a transcanal view, and lack of spontaneous closure at the 6-month follow-up. The exclusion criteria were the presence of cholesteatoma, wet appearance of the mucosa in the tympanic cavity, ear discharge in the 3 months before surgery, or signs of ossicular inconsistency. In-office fat graft myringoplasty technique under local anesthesia. Complete perforation closure rate and audiometric outcomes. A total of 121 patients underwent the procedure, of whom 21 had bilateral sequential procedures (total 142 ears). Average age was 51.1 ± 18.4 years (range, 3-78 years). The size of perforation was In office fat graft myringoplasty, in adult and pediatric patients with variable perforation sizes, is a well-tolerated procedure with very satisfactory clinical results

Non-acid reflux and sleep apnea: the importance of drug induced sleep endoscopy.

We present the first case of a patient with obstructive sleep apnea syndrome (OSA), where drug induced sleep endoscopy was helpful to suspect a non-acid reflux disease and showed an improvement in a swollen epiglottis after treatment. Patient ameliorated significantly his disease only with medical therapy. A 54-year-old man without significant anatomical findings with obstructive sleep apnea syndrome and non-acid gastroesophageal reflux disease (GERD) disease whose Apnea- hypopnea index (AHI) was significantly reduced with the intake of 500 mg of sodium alginate twice a day for 6 months. Conventional digestive tests such as esophagoscopy and simple- and double-channel 24-h pH-metry suggested mild GERD. Conventional proton-pump inhibitor treatment with pantoprazole (40 mg daily) was started without any improvement in his sleep. Multichannel intraluminal 24-h impedanciometry indicated the presence of severe pathological GER of gaseous origin. The patient's AHI decreased from 25.3 at baseline to 8 after treatment with sodium alginate. A drug-induced sleep endoscopy study showed the changes before and after this treatment and was helpful for the diagnosis. Thus, medical treatment can be a therapeutic option in some patients with OSA. Multichannel 24-h impedanciometry should be performed when nonacid GERD is suspected

New mHealth application software based on myofunctional therapy applied to sleep-disordered breathing in non-compliant subjects

Abstract Background Myofunctional therapy (MT) is a therapeutic option with demonstrated efficacy for treating sleep-disordered breathing. We assessed the clinical application of a newly developed m-Health App, which aimed to allow patients with OSAHS (obstructive sleep apnea/hypopnea syndrome) to perform oropharyngeal exercises only by interacting with their smartphone without no other devices. Methods We offered to treat the OSAHS of 20 patients with the App for 90 sessions. Inclusion criteria were adult patients diagnosed with OSAHS who rejected, or could not tolerate or afford treatment for their OSAHS with other modalities. The App was used by 15 patients, while 5 were noncompliant and then were used as a control group. Polygraphy was performed at the beginning of the study, and after 90 sessions in the App group or after 3 months in the control group. Data for adherence to treatment, sex, body mass index (BMI), age, O2MIN (oxygen minimal saturation) and apnea–hypopnea index (AHI) were collected for both groups. Results 15 (75%) patients showed adherence to the treatment as measured as performing the exercises daily 5 days a week. In patients who performed the exercises, AHI decreased from 25.78 ± 12.6 to 14.1 ± 7,7 (p = 0.002), Epworth changed from 18,2 ± 1,98 to 14,2 ± 7,7(p = 0,002) and (O2MIN) changed from 84,87 ± 7.02 to 89,27 ± 3,77 (p = 0.0189). In the control group, there was no significant change. Conclusions To our knowledge, this is the first study reported where a mHealth App based on MT could be by itself a therapeutic option in selected patients with OSAHS

Myofunctional Therapy App for Severe Apnea-Hypopnea Sleep Obstructive Syndrome: Pilot Randomized Controlled Trial.

Myofunctional therapy has demonstrated efficacy in treating sleep-disordered breathing. We assessed the clinical use of a new mobile health (mHealth) app that uses a smartphone to teach patients with severe obstructive sleep apnea-hypopnea syndrome (OSAHS) to perform oropharyngeal exercises. We conducted a pilot randomized trial to evaluate the effects of the app in patients with severe OSAHS. Forty patients with severe OSAHS (apnea-hypoxia index [AHI]>30) were enrolled prospectively and randomized into an intervention group that used the app for 90 sessions or a control group. Anthropometric measures, Epworth Sleepiness Scale (0-24), Pittsburgh Sleep Quality Index (0-21), Iowa Oral Performance Instrument (IOPI) scores, and oxygen desaturation index were measured before and after the intervention. After the intervention, 28 patients remained. No significant changes were observed in the control group; however, the intervention group showed significant improvements in most metrics. AHI decreased by 53.4% from 44.7 (range 33.8-55.6) to 20.88 (14.02-27.7) events/hour (P Orofacial exercises performed using an mHealth app reduced OSAHS severity and symptoms, and represent a promising treatment for OSAHS. Spanish Registry of Clinical Studies AWGAPN-2019-01, ClinicalTrials.gov NCT04438785; https://clinicaltrials.gov/ct2/show/NCT04438785

Ankyloglossia in Children, a Cause of Obstructive Sleep Apnoea: Case Report of Paediatric Ankyloglossia and Sleep Apnoea: DISE Resolves the Mystery

Tongue mobility is an obstructive sleep apnoea (OSA) marker and myofunctional therapy (MFT) target. For this reason, all paediatric patients with sleep-disordered breathing should require a combined functional assessment from an ear, nose, and throat (ENT) specialist and a phonoaudiologist to confirm or rule out the presence of ankyloglossia. To our knowledge, this is the first case of a 13-year-old girl diagnosed with severe OSA and a significant decrease of 94% in her apnoea index (AI), requiring frenotomy with an immediate postoperative change in the tongue position. A drug-induced sleep endoscopy (DISE) was performed before and immediately postfrenotomy, and the anatomical changes provoked by this surgery during sleep were confirmed for the first time